Management of refractory status epilepticus in adults: still more questions than answers

Abstract

Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

Figure 1

Flow chart of status epilepticus treatment*. Increasing refractoriness is illustrated by the background color intensity; the non-sedating agents are green, anesthetics in orange to red, and other options in yellow or white. First-line treatment is light green, second-line darker green, and third line light and darker orange. Other options are given in red, yellow and blue. *Great caution is required for valproate in children under 2 years (hepatic toxicity), and propofol in young children (propofol infusion syndrome). In this setting, benzodiazepines, phenytoin and barbiturates represent the most widely used options. CLZ: clonazepam; ECT: electroconvulsive treatment; KD: ketogenic diet; LCM: lacosamide; LEV: levetiracetam; LZP: lorazepam; MDZ: midazolam; PGB: pregabaline; PHT: phenytoin; PRO: propofol; PTB: pentobarbital; rTMS: repetitive transcranial magnetic stimulation; SE: status epilepticus; THP: thiopental; TPM: topiramate; VNS: vagus nerve stimulation; VPA: valproate.